Mechanistic analysis of the PD-1 blockade combination cancer immunotherapy with BTK inhibitors.

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Acalabrutinib could change the metabolic patterns of CD8+ T cells in vivo, but failed in vitro. Both BTK inhibitors could reduce UPR genes expression in CD8+ T cells, especially for Xbp1s. The expression of Xbp1s was up-regulated in tumor-infiltrating CD8+ T cells compared with those from DLNs and tumor-free LNs. In addition, the Xbp1s expression showed negative correlation with Ifng, Gzmb and Prf1 in tumor-infiltrating CD8+ T cells. Similarly, in vitro experiments revealed that Xbp1s overexpressed CD8+ T cells had lower levels of interferon-gamma, granzyme B and perforin than wild type. By analyzing the GEO dataset GSE118430, we found that Xbp1 KO CD4+ T cells showed relatively high expression of several genes associated with T cells immune response such as Ifng, Ccl5, Cxcr5, etc.